Combination of Dexamethasone and Tofacitinib Reduces Xenogeneic MSC-Induced Immune Responses in a Mouse Model of Alzheimer’s Disease
We have recently reported on how transplantation of human mesenchymal stem cells (MSCs) into the mouse parenchyma generated immune responses. To facilitate the clinical translation of MSC-based AD therapy, the safety and efficacy of human derived MSCs (hMSCs) must be confirmed in the pre-clinical st...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-08-01
|
| Series: | Biomedicines |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2227-9059/10/8/1882 |
| _version_ | 1797432434294259712 |
|---|---|
| author | Na Kyung Lee Su Hyeon Myeong Jung Won Hwang Jason K. Sa Hyo Jin Son Hee Jin Kim Hyemin Jang Jong Wook Chang Duk L. Na |
| author_facet | Na Kyung Lee Su Hyeon Myeong Jung Won Hwang Jason K. Sa Hyo Jin Son Hee Jin Kim Hyemin Jang Jong Wook Chang Duk L. Na |
| author_sort | Na Kyung Lee |
| collection | DOAJ |
| description | We have recently reported on how transplantation of human mesenchymal stem cells (MSCs) into the mouse parenchyma generated immune responses. To facilitate the clinical translation of MSC-based AD therapy, the safety and efficacy of human derived MSCs (hMSCs) must be confirmed in the pre-clinical stage. Thus, it is imperative to investigate measures to reduce immune responses exerted via xenotransplantation. In this study, immunosuppressants were co-administered to mice that had received injections of hMSCs into the parenchyma. Prior to performing experiments using transgenic AD mice (5xFAD), varying immunosuppressant regimens were tested in wild-type (WT) mice and the combination of dexamethasone and tofacitinib (DexaTofa) revealed to be effective in enhancing the persistence of hMSCs. According to transcriptome sequencing and immunohistochemical analyses, administration of DexaTofa reduced immune responses generated via transplantation of hMSCs in the parenchyma of 5xFAD mice. Significant mitigation of amyloid burden, however, was not noted following transplantation of hMSCs alone or hMSCs with DexaTofa. The efficacy of the immunosuppressant regimen should be tested in multiple AD mouse models to promote its successful application and use in AD stem cell therapy. |
| first_indexed | 2024-03-09T10:00:29Z |
| format | Article |
| id | doaj.art-73cbd12a854b462e841637675679898c |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-09T10:00:29Z |
| publishDate | 2022-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-73cbd12a854b462e841637675679898c2023-12-01T23:27:38ZengMDPI AGBiomedicines2227-90592022-08-01108188210.3390/biomedicines10081882Combination of Dexamethasone and Tofacitinib Reduces Xenogeneic MSC-Induced Immune Responses in a Mouse Model of Alzheimer’s DiseaseNa Kyung Lee0Su Hyeon Myeong1Jung Won Hwang2Jason K. Sa3Hyo Jin Son4Hee Jin Kim5Hyemin Jang6Jong Wook Chang7Duk L. Na8School of Medicine, Sungkyunkwan University, Suwon 16419, KoreaSamsung Medical Center, Cell and Gene Therapy Institute (CGTI), Research Institute for Future Medicine, Seoul 06351, KoreaDepartment of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences & Technology (SAIHST), Sungkyunkwan University, Seoul 06351, KoreaDepartment of Biomedical Sciences, Korea University College of Medicine, Seoul 02841, KoreaSchool of Medicine, Sungkyunkwan University, Suwon 16419, KoreaSamsung Medical Center, Cell and Gene Therapy Institute (CGTI), Research Institute for Future Medicine, Seoul 06351, KoreaSamsung Medical Center, Cell and Gene Therapy Institute (CGTI), Research Institute for Future Medicine, Seoul 06351, KoreaSamsung Medical Center, Cell and Gene Therapy Institute (CGTI), Research Institute for Future Medicine, Seoul 06351, KoreaSamsung Medical Center, Cell and Gene Therapy Institute (CGTI), Research Institute for Future Medicine, Seoul 06351, KoreaWe have recently reported on how transplantation of human mesenchymal stem cells (MSCs) into the mouse parenchyma generated immune responses. To facilitate the clinical translation of MSC-based AD therapy, the safety and efficacy of human derived MSCs (hMSCs) must be confirmed in the pre-clinical stage. Thus, it is imperative to investigate measures to reduce immune responses exerted via xenotransplantation. In this study, immunosuppressants were co-administered to mice that had received injections of hMSCs into the parenchyma. Prior to performing experiments using transgenic AD mice (5xFAD), varying immunosuppressant regimens were tested in wild-type (WT) mice and the combination of dexamethasone and tofacitinib (DexaTofa) revealed to be effective in enhancing the persistence of hMSCs. According to transcriptome sequencing and immunohistochemical analyses, administration of DexaTofa reduced immune responses generated via transplantation of hMSCs in the parenchyma of 5xFAD mice. Significant mitigation of amyloid burden, however, was not noted following transplantation of hMSCs alone or hMSCs with DexaTofa. The efficacy of the immunosuppressant regimen should be tested in multiple AD mouse models to promote its successful application and use in AD stem cell therapy.https://www.mdpi.com/2227-9059/10/8/1882immunosuppressantAlzheimer’s diseasedexamethasonetofacitinibimmune response |
| spellingShingle | Na Kyung Lee Su Hyeon Myeong Jung Won Hwang Jason K. Sa Hyo Jin Son Hee Jin Kim Hyemin Jang Jong Wook Chang Duk L. Na Combination of Dexamethasone and Tofacitinib Reduces Xenogeneic MSC-Induced Immune Responses in a Mouse Model of Alzheimer’s Disease Biomedicines immunosuppressant Alzheimer’s disease dexamethasone tofacitinib immune response |
| title | Combination of Dexamethasone and Tofacitinib Reduces Xenogeneic MSC-Induced Immune Responses in a Mouse Model of Alzheimer’s Disease |
| title_full | Combination of Dexamethasone and Tofacitinib Reduces Xenogeneic MSC-Induced Immune Responses in a Mouse Model of Alzheimer’s Disease |
| title_fullStr | Combination of Dexamethasone and Tofacitinib Reduces Xenogeneic MSC-Induced Immune Responses in a Mouse Model of Alzheimer’s Disease |
| title_full_unstemmed | Combination of Dexamethasone and Tofacitinib Reduces Xenogeneic MSC-Induced Immune Responses in a Mouse Model of Alzheimer’s Disease |
| title_short | Combination of Dexamethasone and Tofacitinib Reduces Xenogeneic MSC-Induced Immune Responses in a Mouse Model of Alzheimer’s Disease |
| title_sort | combination of dexamethasone and tofacitinib reduces xenogeneic msc induced immune responses in a mouse model of alzheimer s disease |
| topic | immunosuppressant Alzheimer’s disease dexamethasone tofacitinib immune response |
| url | https://www.mdpi.com/2227-9059/10/8/1882 |
| work_keys_str_mv | AT nakyunglee combinationofdexamethasoneandtofacitinibreducesxenogeneicmscinducedimmuneresponsesinamousemodelofalzheimersdisease AT suhyeonmyeong combinationofdexamethasoneandtofacitinibreducesxenogeneicmscinducedimmuneresponsesinamousemodelofalzheimersdisease AT jungwonhwang combinationofdexamethasoneandtofacitinibreducesxenogeneicmscinducedimmuneresponsesinamousemodelofalzheimersdisease AT jasonksa combinationofdexamethasoneandtofacitinibreducesxenogeneicmscinducedimmuneresponsesinamousemodelofalzheimersdisease AT hyojinson combinationofdexamethasoneandtofacitinibreducesxenogeneicmscinducedimmuneresponsesinamousemodelofalzheimersdisease AT heejinkim combinationofdexamethasoneandtofacitinibreducesxenogeneicmscinducedimmuneresponsesinamousemodelofalzheimersdisease AT hyeminjang combinationofdexamethasoneandtofacitinibreducesxenogeneicmscinducedimmuneresponsesinamousemodelofalzheimersdisease AT jongwookchang combinationofdexamethasoneandtofacitinibreducesxenogeneicmscinducedimmuneresponsesinamousemodelofalzheimersdisease AT duklna combinationofdexamethasoneandtofacitinibreducesxenogeneicmscinducedimmuneresponsesinamousemodelofalzheimersdisease |